Comparing Sedatives for Intracranial Pressure Control in Traumatic Brain Injury (ICP-TBI)
Effect of Propofol, Midazolam, and Dexmedetomidine on Intracranial Pressure and Clinical Outcomes in Patients With Moderate-to-Severe Traumatic Brain Injury Undergoing Urgent Neurosurgical Intervention
The goal of this clinical trial is to compare the effects of propofol, midazolam, and dexmedetomidine on intracranial pressure control and clinical outcomes in adults with moderate-to-severe traumatic brain injury undergoing urgent neurosurgical intervention.
The main questions it aims to answer are:
- Which sedative agent provides better control of intracranial pressure, assessed by optic nerve sheath diameter (ONSD), during the first 24 hours after neurosurgical intervention?
- How do the three sedative agents compare in achieving target sedation depth, maintaining hemodynamic stability, and improving short-term clinical outcomes such as ICU mortality, duration of mechanical ventilation, and ICU length of stay?
Participants will be randomly assigned to receive propofol, midazolam, or dexmedetomidine for 24 hours of continuous sedation. Clinical, hemodynamic, and neurological outcomes will be assessed and compared among the three study groups.
調査の概要
状態
詳細な説明
Traumatic brain injury (TBI) is a major cause of mortality and long-term disability worldwide. Prevention of secondary brain injury through optimal control of intracranial pressure (ICP) is a key component of intensive care management in patients with moderate-to-severe TBI. Sedative agents are routinely used to facilitate mechanical ventilation, reduce cerebral metabolic demand, and improve ICP control. However, uncertainty remains regarding the optimal sedative agent for this patient population.
Propofol, midazolam, and dexmedetomidine are among the most commonly used sedatives in neurocritical care. Each agent has distinct pharmacological characteristics that may influence intracranial pressure, hemodynamic stability, neurological assessment, and clinical outcomes. Despite widespread use, direct comparative evidence between these agents remains limited.
This prospective randomized clinical trial aims to compare the effects of propofol, midazolam, and dexmedetomidine on intracranial pressure control and clinical outcomes in adult patients with moderate-to-severe traumatic brain injury undergoing urgent neurosurgical intervention. Intracranial pressure will be assessed noninvasively using serial optic nerve sheath diameter (ONSD) measurements obtained by ocular ultrasonography during the first 24 hours of continuous sedation.
Participants will be randomly assigned to receive one of the three sedative regimens according to a standardized protocol targeting a Richmond Agitation-Sedation Scale (RASS) score of -3 to -4. Standard neurocritical care management and analgesia protocols will be applied to all study groups.
The study will evaluate the comparative effects of the three sedative agents on intracranial pressure control, sedation quality, hemodynamic stability, adverse events, secondary brain injury, and short-term clinical outcomes. The findings are expected to provide evidence to guide sedative selection in patients with moderate-to-severe traumatic brain injury, particularly in settings where invasive intracranial pressure monitoring is not routinely available.
研究の種類
入学 (推定)
段階
- 適用できない
連絡先と場所
研究連絡先
- 名前：Mohamed Abdelhamed, M.Sc
- 電話番号：+201061651065
- メール：mohamed.said@med.aswu.edu.eg
研究場所
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-
Asyut Governorate
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Asyut、Asyut Governorate、エジプト、81528
- Aswan university hospital
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コンタクト：
- Mohamed Abdelhamed, M.Sc.
- 電話番号：01061651065
- メール：hamedo_2020@yahoo.com
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-
参加基準
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
説明
Inclusion Criteria:
Age ≥18 years
- Moderate to severe traumatic brain injury with post-resuscitation Glasgow Coma Scale (GCS) ≤12
- Undergone urgent neurosurgical intervention (craniotomy, craniectomy, or ICP monitor placement) within 24 hours of injury
- Admitted to ICU and expected to require continuous sedation
- Hemodynamically stable or stabilized (defined as MAP ≥65 mmHg with vasopressor requirement ≤0.1 mcg/kg/min norepinephrine equivalent)
- Informed consent obtained from legally authorized representative
Exclusion Criteria:
- The Relative refusal to participate in the research.
- Known allergy or contraindication to propofol, midazolam, or dexmedetomidine
- Pre-existing neurological disorders (epilepsy, prior stroke, brain tumors, dementia) that may interfere with outcome assessment
- Severe hepatic dysfunction (Child-Pugh Class C) or acute liver failure
- Severe renal dysfunction (eGFR <30 mL/min/1.73m² or requiring renal replacement therapy)
- Pregnancy or breastfeeding
- Hemodynamic instability requiring norepinephrine >0.1 mcg/kg/min or equivalent vasopressor support
- Heart rate <50 bpm or second/third-degree AV block without pacemaker (relative contraindication for dexmedetomidine)
- Clinical determination of brain death or expected survival <24 hours
- Enrollment in another interventional trial
- Severe polytrauma requiring ongoing surgical interventions that would interfere with protocol adherence
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：独身
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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実験的：Propofol
Participants receive continuous intravenous propofol infusion initiated at 1 mg/kg/h and titrated to 1-4 mg/kg/h to maintain a target RASS score of -3 to -4 for 24 hours.
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Continuous intravenous propofol infusion initiated at 1 mg/kg/h and titrated within a range of 1-4 mg/kg/h to maintain a target Richmond Agitation-Sedation Scale (RASS) score of -3 to -4 during the 24-hour study intervention period.
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実験的：Midazolam
Participants receive continuous intravenous midazolam infusion initiated at 0.03 mg/kg/h and titrated to 0.02-0.1 mg/kg/h to maintain a target RASS score of -3 to -4 for 24 hours.
|
Continuous intravenous midazolam infusion initiated at 0.03 mg/kg/h and titrated within a range of 0.02-0.1 mg/kg/h to maintain a target Richmond Agitation-Sedation Scale (RASS) score of -3 to -4 during the 24-hour study intervention period.
An initial bolus dose of 0.05 mg/kg may be administered if rapid sedation is required.
|
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実験的：dexmedetomidine
Participants receive continuous intravenous dexmedetomidine infusion initiated at 0.4 μg/kg/h and titrated to 0.2-0.7 μg/kg/h to maintain a target RASS score of -3 to -4 for 24 hours.
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Continuous intravenous dexmedetomidine infusion initiated at 0.4 μg/kg/h and titrated within a range of 0.2-0.7 μg/kg/h to maintain a target Richmond Agitation-Sedation Scale (RASS) score of -3 to -4 during the 24-hour study intervention period.
No loading dose will be administered.
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Intracranial Pressure Control Assessed by Optic Nerve Sheath Diameter (ONSD)
時間枠：Baseline, 6 hours, 12 hours, and 24 hours after initiation of sedation
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Intracranial pressure control will be evaluated using serial optic nerve sheath diameter (ONSD) measurements obtained by ocular ultrasonography.
The primary outcome will be the mean ONSD over the 24-hour intervention period, analyzed as a continuous measure of intracranial pressure control.
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Baseline, 6 hours, 12 hours, and 24 hours after initiation of sedation
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Proportion of Time at Target Sedation Level
時間枠：24 hours after initiation of sedation
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Percentage of assessment time during which patients maintained the target Richmond Agitation-Sedation Scale (RASS) score of -3 to -4.
The Richmond Agitation-Sedation Scale ranges from +4 (combative) to -5 (unarousable).
Higher scores indicate greater agitation, whereas lower scores indicate deeper sedation.
The target sedation level for this study is RASS -3 to -4.
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24 hours after initiation of sedation
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Mean Richmond Agitation-Sedation Scale (RASS) Score
時間枠：24 hours after initiation of sedation
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Mean Richmond Agitation-Sedation Scale (RASS) score during the 24-hour intervention period.
The RASS ranges from +4 (combative) to -5 (unarousable), with target sedation defined as -3 to -4.
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24 hours after initiation of sedation
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Need for Rescue Sedation
時間枠：24 hours after initiation of sedation
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Proportion of patients requiring rescue sedation due to failure to achieve target sedation despite maximum protocol dose.
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24 hours after initiation of sedation
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Time to Achieve Target Sedation
時間枠：24 hours after initiation of sedation
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Time from initiation of study sedative infusion until achievement of target Richmond Agitation-Sedation Scale (RASS) score (-3 to -4).The RASS ranges from +4 (combative) to -5 (unarousable)
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24 hours after initiation of sedation
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Incidence of Hypotension
時間枠：24 hours after initiation of study sedation
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Incidence of hypotension, defined as mean arterial pressure (MAP) <65 mmHg or cerebral perfusion pressure (CPP) <60 mmHg.
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24 hours after initiation of study sedation
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Vasopressor Requirements
時間枠：24 hours after initiation of study sedation.
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Vasopressor requirements assessed by the proportion of patients requiring vasopressor support.
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24 hours after initiation of study sedation.
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Incidence of Bradycardia.
時間枠：24 hours after initiation of study sedation.
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Percentage of participants who develop bradycardia, defined as a sustained heart rate <50 beats per minute (bpm).
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24 hours after initiation of study sedation.
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Percentage of Participants Who Developed Secondary Brain Injury ✅
時間枠：Baseline and 24 hours after initiation of study sedation.
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Secondary brain injury will be assessed by the presence of new or progressive findings on brain computed tomography (CT) compared with baseline imaging, including new intracranial hemorrhage, progression of cerebral edema (defined as >25% increase in midline shift or worsening basal cistern effacement), new cerebral infarction, or transtentorial or uncal herniation.
Brain CT scans will be reviewed by a blinded neuroradiologist.
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Baseline and 24 hours after initiation of study sedation.
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Duration of Mechanical Ventilation
時間枠：From initiation of mechanical ventilation until successful extubation, assessed for up to 30 days.
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Duration of invasive mechanical ventilation, measured as the number of days from initiation of mechanical ventilation until successful liberation from ventilatory support.
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From initiation of mechanical ventilation until successful extubation, assessed for up to 30 days.
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Time to Neurological Awakening
時間枠：From discontinuation of study sedation until achievement of a Glasgow Coma Scale motor score of ≥5, assessed for up to 30 days.
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Time from discontinuation of study sedation to achievement of a Glasgow Coma Scale (GCS) motor score of ≥5.
The Glasgow Coma Scale motor component ranges from 1 (no motor response) to 6 (obeys commands), with higher scores indicating better neurological function.
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From discontinuation of study sedation until achievement of a Glasgow Coma Scale motor score of ≥5, assessed for up to 30 days.
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ICU Mortality
時間枠：From ICU admission until ICU discharge, assessed for up to 30 days.
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Death from any cause during the ICU stay following urgent neurosurgical intervention for traumatic brain injury.
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From ICU admission until ICU discharge, assessed for up to 30 days.
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協力者と研究者
スポンサー
捜査官
- スタディチェア：Ahmed Elsaied Aly, Ph.D.、Sohag University
研究記録日
主要日程の研究
研究開始 (推定)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- 1230/3/26
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